Neuroprotective effects of PPAR-γ agonist rosiglitazone in N171-82Q mouse model of Huntington's disease.
Neuroprotective effects of PPAR-γ agonist rosiglitazone in N171-82Q mouse model of Huntington's disease.
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DOI：
10.1111/jnc.12190
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发表时间：
2013-05
影响因子：
4.7
通讯作者：
Duan W
中科院分区：
文献类型：
--
作者：
Jin J;Albertz J;Guo Z;Peng Q;Rudow G;Troncoso JC;Ross CA;Duan W
Huntington’s disease (HD) is a devastating genetic neurodegenerative disease caused by CAG trinucleotide expansion in the exon-1 region of the huntingtin gene. Currently, no cure is available. It is becoming increasingly apparent that mutant HTT impairs metabolic homeostasis and causes transcriptional dysregulation. The peroxisome proliferator-activated receptor gamma (PPAR-γ) is a transcriptional factor that plays a key role in regulating genes involved in energy metabolism; recent studies demonstrated that PPAR-γ activation prevented mitochondrial depolarization in cells expressing mutant HTT and attenuated neurodegeneration in various models of neurodegenerative diseases. PPAR-γ-coactivator 1α (PGC-1 α) transcription activity is also impaired by mutant HTT. We now report that the PPAR-γ agonist, rosiglitazone (RSG), significantly attenuated mutant HTT-induced toxicity in striatal cells and that the protective effect of RSG is mediated by activation of PPAR-γ. Moreover, chronic administration of RSG (10 mg/kg/d, i.p) significantly improved motor function and attenuated hyperglycemia in N171-82Q HD mice. RSG administration rescued BDNF deficiency in the cerebral cortex, and prevented loss of orexin-A-immunopositive neurons in the hypothalamus of N171-82Q HD mice. RSG also prevented PGC-1α reduction and increased Sirt6 protein levels in HD mouse brain. Our results suggest that modifying the PPAR-γ pathway plays a beneficial role in rescuing motor function as well as glucose metabolic abnormalities in HD.
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影响因子：
4.7
作者：
Chou, SY;Lee, YC;Chern, YJ
通讯作者：
Chern, YJ
DOI：
10.1016/j.bbadis.2011.05.006
发表时间：
2011-09-01
影响因子：
6.2
作者：
Chiang, Ming-Chang;Chern, Yijuang;Juo, Chiun-Gung
通讯作者：
Juo, Chiun-Gung
影响因子：
3.3
作者：
Carta, A. R.;Frau, L.;Carboni, E.
通讯作者：
Carboni, E.
影响因子：
3.7
作者：
Fatehi-Hassanabad, Zahra;Tasker, R. A.
通讯作者：
Tasker, R. A.
影响因子：
82.9
作者：
Jiang M;Wang J;Fu J;Du L;Jeong H;West T;Xiang L;Peng Q;Hou Z;Cai H;Seredenina T;Arbez N;Zhu S;Sommers K;Qian J;Zhang J;Mori S;Yang XW;Tamashiro KL;Aja S;Moran TH;Luthi-Carter R;Martin B;Maudsley S;Mattson MP;Cichewicz RH;Ross CA;Holtzman DM;Krainc D;Duan W
通讯作者：
Duan W